Betulin attenuated liver damage by prevention of hepatic mitochondrial dysfunction in rats with alcoholic steatohepatitis

Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4 g/kg, intragastric) for 8 weeks. The treatment with betulin (50 and 100 mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100 mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition

Ferutinin Induces Membrane Depolarization, Permeability Transition Pore Formation, and Respiration Uncoupling in Isolated Rat Liver Mitochondria by Stimulation of Ca 2+ -Permeability

It is well known that the terpenoid ferutinin (4-oxy-6-(4-oxybenzoyloxy) dauc-8,9-en), isolated from the plant Ferula tenuisecta, considerably increases the permeability of artificial and cellular membranes to Ca2+-ions and produces apoptotic cell death in different cell lines in a mitochondria-dependent manner. The present study was designed for further evaluation of the mechanism(s) of mitochondrial effects of ferutinin using isolated rat liver mitochondria. Our findings provide evidence for ferutinin at concentrations of 5–27 µM to decrease state 3 respiration and the acceptor control ratio in the case of glutamate/malate as substrates. Ferutinin alone (10–60 µM) also dose-dependently dissipated membrane potential. In the presence of Ca2+-ions, ferutinin (10–60 µM) induced considerable depolarization of the inner mitochondrial membrane, which was partially inhibited by EGTA, and permeability transition pore formation, which was diminished partly by cyclosporin A, and did not influence markedly the effect of Ca2+ on mitochondrial respiration. Ruthenium Red, a specific inhibitor of mitochondrial calcium uniporter, completely inhibited Ca2+ -induced mitochondria swelling and membrane depolarization, but did not affect markedly the stimulation of these Ca2+-dependent processes by ferutinin. We concluded that the mitochondrial effects of ferutinin might be primarily induced by stimulation of mitochondrial membrane Ca2+-permeability, but other mechanisms, such as driving of univalent cations, might be involved

Furyl(aryl)alkanes and Their Derivatives. 19. Synthesis of Benzofuran Derivatives via 2-Hydroxyaryl-R-(5-methylfur-2-yl)methanes. Reaction of Furan Ring Opening - Benzofuran Ring Closure Type

2-Hydroxyaryl(5-methylfur-2-yl)alkanes synthesized by alkylation of 2-methylfuran with various 2-hydroxybenzylic alcohols, were rearranged into corresponding 3-R-benzo[b]furan derivatives by treatment with ethanolic HCl solution. These compounds can not be transformed into dibenzoxazulenium salts